F. Miranda notes that this surname, together with its variants (Spitalieri, Spitalere, Spitaliere, Spedaliere), derives from the word spedaliere, which designated one who worked in a hospital. According to the role required by need, he could be manager, nurse, watchman, custodian or service staff in structures of hospitality that fulfilled various functions: care of the sick, asylum for the poor, the elderly and foundlings, and refuge for travellers and strangers.

G. P. Holmes links the term to the medieval Latin hospitalarius, derived from hospitium, a word used to designate the structures of welcome for travellers and strangers, as well as asylums for orphans. The hospitalarius was, therefore, the person responsible for such establishments.

V. Blunda highlights its Sicilian and dialectal character: it comes from the word spitalèri, meaning "hospital servant", and designates the employee in charge of the care of the sick in the assistance establishments of Sicily. According to this author, the surname could have originated in an occupational nickname applied to one who devoted himself to that service of institutional hospitality.

As for its geographical distribution, Miranda documents its presence in Sicily in an extended way, in all its provinces, with a greater concentration in the Catania area, followed by Palermo, Messina, Enna, Syracuse, Agrigento, Caltanissetta, Trapani and Ragusa. In the Enna area it is recorded in localities such as Troina, Valguarnera Caropepe, Leonforte, Centuripe, Agira, Nicosia, Regalbuto, Catenanuova and Piazza Armerina. Outside Sicily, it also appears in Lombardy, Piedmont, Lazio, Tuscany, Liguria, Veneto and Emilia-Romagna, though with a more limited presence.